Peter Gøtzsche: Cipriani review does not add anything

This huge systematic review (Cipriani et al 2018) does not add anything to the knowledge we already had about depression pills.

Briefly, the effects as estimated on the Hamilton scale are very similar to those reported in a another huge meta-analysis in early 2017 (Jakobsen JC, Katakam KK, Schou A, et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry 2017;17:58). See p4 bottom right and p150 in the Appendix for these results. The average effect of these drugs, SMD 0.30, is less than what is clinically relevant.

There were two primary outcomes, response rate and drop-out for any reason.

As explained in the Discussion of Jakobsen’s meta-analysis, response rates, defined as “the total number of patients who had a reduction of ≥50% of the total score on a standardised observer-rating scale for depression”, are flawed and should not be trusted.

The other primary outcome was called acceptability in the paper, defined as treatment discontinuation measured by the proportion of patients who withdrew for any reason. The results for this outcome are shown in Figure 3 and on p148 in the Appendix. They are not reliable. We have done such an analysis based on clinical study reports of placebo-controlled trials we have obtained from European drug regulators (submitted for publication). I will not reveal the details before our results have been published, but our results are very different from those shown in the Lancet paper. The use of clinical study reports is crucial. The manufactures had excluded patients from their analyses, which we were able to include. This is generally not possible for the type of systematic review done by Cipriani et al. So, these results are also flawed and should not be trusted.

I agree with Peter, and with Joanna’s post about this. It is very disappointing that the response has been so uncritical both professionally, and in the press. It does make one despondent about people’s appreciation of critical analysis. I am rather surprised to see JI’s association with the study. You may like to see my fairly substantive criticism on my websitehttps://psychotropical.info/lancet-21-antidepressants-meta-analysis/

It is very interesting that the drug industry and psychiatry now feel that they have to defend their drugs. That means that the wind is changing. They are not going forward with optimism, but they have to defend themselves.
Those of us who feel that the science behind this should be known by everybody, should use all the tools we have available for letting people now know the facts.

Depression drugs are compared to cold turkey withdrawal in the placebo group. Even if people in the placebo group are in total abstinence from their previous drug, they do so well without their drug that neither patients nor doctors would be able to know the difference. The placebo group gets as good results as the drug group one week later.

The drugs are not tested on the people who will actually use them. This is like testing drugs against pneumonia and patients who have stomach problems. 90% of the patients will take depression drugs, or not the patients that the drugs have been tested on. This means that we have no evidence base for using these drugs for 90% of the patients were taking them.

Depression drugs are tested by the companies that make them. This is like Pepsi testing if Pepsi is better than Coca Cola or a mobster being judged with only family members in the jury or a judge asking the accused to provide condemning evidence in his own trial. In all other areas of life we disregard the results that come from these kind of testifying on your own behalf.